Mesenchymal miR-21 regulates branching morphogenesis in murine submandibular gland in vitro
Mesenchymal miR-21 regulates branching morphogenesis in murine submandibular gland in vitro
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DOI：
10.1016/j.ydbio.2011.01.030
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发表时间：
2011-04-15
影响因子：
2.7
通讯作者：
Kashimata, Masanori
中科院分区：
文献类型：
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作者：
Hayashi, Toru;Koyama, Noriko;Kashimata, Masanori
小鼠下颌下腺(SMG)的分支形态发生受生长因子、细胞外基质(ECM)和许多生物学过程的调控，这些过程是通过上皮和间质之间的相互作用来实现的。MicroRNAs(MiRNAs)是一组小的、非蛋白质编码的RNA，在转录后水平上调节基因的表达。我们假设分支形态发生部分受miRNAs调控。在胚胎第13天，用克隆方法结合Argavite-2免疫沉淀方法在SMG中检测到44个miRNAs和新的miRNA候选基因。MicroRNA21(miR-21)在间质中的表达被表皮生长因子上调和加速，这是已知的促进体外分支形态发生的因素。锁定的核酸下调间充质中miR-21的表达与上皮芽的数量减少有关。对miR-21靶基因候选基因的相对定量表明，两个信使RNA(针对RECK和Pdcd4)在间充质中下调，miR-21的表达水平上调。这些结果表明，miR-21通过与间充质中ECM降解相关的基因表达来调控分枝形态发生。(C)2011 Elsevier Inc.保留所有权利。
Branching morphogenesis in murine submandibular glands (SMG) is regulated by growth factors, extracellular matrix (ECM) and many biological processes through interactions between the epithelium and the mesenchyme. MicroRNAs (miRNAs) are a set of small, non-protein-coding RNAs that regulate gene expression at the post-transcriptional level. We hypothesized that branching morphogenesis is partly regulated by miRNAs. Forty-four miRNAs and novel miRNA candidates were detected in SMG at embryonic day 13 by a cloning method combined with Argonaute-2 immunoprecipitation. MicroRNA21 (miR-21) expression in the mesenchyme was up-regulated and accelerated by epidermal growth factor, which is known to enhance branching morphogenesis in vitro. Down-regulation of miR-21 in the mesenchyme by locked nucleic acids was associated with a decrease in the number of epithelial buds. Relative quantification of candidates for target genes of miR-21 indicated that two messenger RNAs (for Reck and Pdcd4) were down-regulated in the mesenchyme, where miR-21 expression levels were up-regulated. These results suggest that branching morphogenesis is regulated by miR-21 through gene expression related to ECM degradation in the mesenchyme. (C) 2011 Elsevier Inc. All rights reserved.